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SIMVASTATIN AMMELIORATES THE INCREASED HEPATIC VASCULAR TONE IN PATIENTS WITH
CIRRHOSIS
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C. Zafra, J.G. Abraldes*, C. Cortez, A. Berzigotti, I. Tarantino, J.C.
Garcia-Pagan, J. Bosch,
*Presenting Author Hepatic Hemodynamic Laboratory. Liver Unit. Hospital
Clinic. IDIBAPS. University Of Barcelona., Barcelona, Spain
An insufficient intrahepatic production of NO in cirrhotic liver contributes
to increase hepatic resistance and portal hypertension, and enhances the
postprandial increase in portal pressure. Simvastatin increases NO production
by enhancing AKT-dependent eNOS phosphorylation. Therefore, simvastatin may
decrease hepatic resistance in cirrhosis. This was evaluated in a group of
patients with cirrhosis and portal hypertension. Methods: Protocol 1. 13
patients had measurements of mean arterial pressure, cardiac output, systemic
vascular resistance, HVPG and hepatic blood flow (HBF) before and 30 and 60
min after receiving 40 mg of simvastatin. Protocol 2. 17 patients were
randomized to receive placebo or simvastatin (40mg) 12 h and 1 h before the
study. After baseline measurements, a standard liquid meal was given and
measurements were repeated at 15, 30 and 45 min. Results: Protocol 1. Acute
simvastatin did not modify HVPG but increased HBF (+21± 13% and +14± 23% at
30 and 60 min respectively;p=0.04) and decreased estimated hepatic sinusoidal
resistance by 14±11% and 11±17% (p=0.01). Systemic hemodynamics were not
modified. Protocol 2. With respect to placebo, pretreatment with simvastatin
significantly attenuated the postprandial increase in portal pressure (+8±8%
vs +17±7% at 15 min, +6±6% vs +18±8% at 30 min, +8±9 vs +15±8% at 45
min;p=0.03). HBF increased equally in the two groups. Hepatic resistance
decreased in simvastatin group but not in placebo
(-17±10% vs -5±8% at 30 min;p=0, 03). Conclusions: Simvastatin effectively
decreases hepatic resistance in patients with cirrhosis, without deleterious
effects on systemic circulation.
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